The U.S. Food and Drug Administration (FDA) has approved the supplemental New Drug Application (sNDA) of brexpiprazole (REXULTI®, Otsuka and Lundbeck) for the treatment of agitation associated with Alzheimer’s dementia (AAD). This is the first FDA-approved treatment indicated for AAD in the United States.

The sNDA approval was based on data from two positive clinical phase 3, 12-week, multicenter, randomized, double-blind, placebo-controlled studies that investigated the treatment of brexpiprazole in patients with AAD (Study 331-12-283 and Study 331-14-213). The primary endpoint for both studies was the change from baseline in the Cohen-Mansfield Agitation Inventory (CMAI) total score at week 12. The CMAI measures the frequency of manifestations of 29 agitated behaviors in elderly persons, such as pacing, restlessness, yelling, and hitting.

Study 331-12-283 was designed to assess the efficacy, safety, and tolerability of brexpiprazole compared with placebo. Results showed brexpiprazole 2 mg/day demonstrated statistically significantly greater improvement in CMAI Total score from baseline to Week 12 than placebo (adjusted mean difference, -3.77; confidence limits, –7.38, –0.17; t(316)?=?–2.06; p?=?0.040; MMRM). In Study 331-14-213, treatment with brexpiprazole 2 and 3 mg/day showed statistically significant improvement compared with placebo for the primary efficacy endpoint, the mean change in CMAI Total Score from baseline to Week 12 (p < 0.05). The improvements from baseline on the primary endpoint of CMAI for patients receiving brexpiprazole 2 mg/day or 3 mg/day were statistically greater than for those receiving placebo (brexpiprazole = -22.6, placebo = -17.3; p = 0.0026). An assessment of mortality risk across clinical trials showed that the effect of brexpiprazole appeared to be consistent with the risk associated with other antipsychotics used in elderly patients with dementia. Treatment emergent adverse events that occurred in at least 2% of brexpiprazole-treated patients and more than with placebo were insomnia, somnolence, nasopharyngitis, and urinary tract infection.

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